Main results

Ivabradine resulted in a rapid decline of heart rate, which was sustained through the study period. Placebo showed a small decline and remained at this higher heart rate.

E/e’ ratio did not significantly change from baseline to end of study in patients treated with ivabradine (n=83) or placebo (n=83), nor did the groups differ significantly.

6MWT did not improve from baseline to end of study in either treatment group, and both groups showed similar distances.

NT-proBNP did not change significantly from baseline to the last measurement in either treatment group, nor did the treatment groups significantly differ.

Numerically more adverse events (AEs) were seen, including serious AEs, but this difference did not reach statistical significance.

Conclusion

These study data show that ivabradine does not benefit HFpEF patients. This might be the consequence of the fact that the population enrolled had rather advanced HFpEF with extensive myocardial fibrosis. Another explanation may lie in the lack of sufficient power due to screening failures, although no significant improvements were seen in the co-secondary endpoints. Moreover, it is possible that a particular phenotype was selected (sinus rhythm), which does not reflect the various subcategories of HFpEF patients.

Thus, it was concluded that in the EDIFY study population, HR reduction with ivabradine did not show a beneficial effect on cardiac filling pressure (E/e’), exercise capacity (6MWD) and plasma NT-proBNP concentrations over 8 months. Hence, these findings do not support the use of ivabradine in this type of patients with HFpEF. Further studies may explore whether other HFpEF phenotypes may benefit from HR reduction. In these data, no subgroups were identified that benefitted from ivabradine.

Discussant Gerasimos Filippatos (Athens, Greece) noted that indeed HFpEF is difficult to treat because it is such a heterogeneous population. Also, he said that it is difficult to see an improvement in NT-proBNP if the mean was between 300 and 400 pf/mL, and 6MWD was around 320 meters, which is quite good for patients aged 72-73 on average.

Furthermore, he questioned whether we know that the HR target is the same in HFpEF as in HFrEF, and whether 8 months is enough to see an effect of reverse modelling. Again, the conclusion is that a lot remains unknown about HFpEF.

Disclosures

Our coverage of ESC HF 2017 is based on the information provided during the congress.